Prostate cancer remains a major public health challenge, with an anticipated 219,000 new cases to be diagnosed this year in the United States and 27,000 deaths expected from the disease (Jemal, et al. CA Cancer J. Clin. 57:43-66 (2007)). The absence of effective treatment for advanced disease reflects, in part, the lack of a detailed understanding of the molecular pathogenesis of prostate cancer. A striking recent discovery, however, indicates that 40-70% of men diagnosed with prostate cancer harbor an acquired chromosomal translocation that results in the fusion of the promoter region of the Transmembrane protease, serine 2 (TMPRSS2) gene to the coding region of members of the erythroblast transformation specific (ETS) family of transcription factors, most commonly V-ets erythroblastosis virus E26 oncogene homolog (avian) (ERG) (Tomlins, et al., Cancer Res. 66:3396-400 (2006); Tomlins, et al., Science 310:644-648 (2005)). TMPRSS2-ERG fusion prostate cancers appear to have a more aggressive natural clinical history (Demichelis, et al., Oncogene 2007)). The downstream effects of TMPRSS2-ERG have yet to be identified, and the mechanism by which TMPRSS2-ERG contributes to the pathogenesis of prostate cancer is entirely unknown. A significant challenge is therefore to identify therapeutic strategies for the manipulation of TMPRSS2-ERG function in prostate cancer cells.